[4-(8-氯-5,6-二氢-11H-苯并[5,6]环庚[1,2-b]吡啶基-11亚烷基)-1-哌啶基](1H-1,2,4-三唑-1-基)甲酮 | 1680193-80-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 中文名称: [4-(8-氯-5,6-二氢-11H-苯并[5,6]环庚[1,2-b]吡啶基-11亚烷基)-1-哌啶基](1H-1,2,4-三唑-1-基)甲酮
• 英文名称: (4-(8-chloro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(6H)-ylidene)piperidin-1-yl)(1H-1,2,4-triazol-1-yl)methanone
• 英文别名: JZP-361；[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]-(1,2,4-triazol-1-yl)methanone
• CAS: 1680193-80-9
• 化学式: C₂₂H₂₀ClN₅O
• 分子量: 405.887
• InChiKey: GAVZCGTYRWKKDV-UHFFFAOYSA-N

物化性质

• 熔点：
  177-177.9°C
• 沸点：
  611.7±65.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  63.9
• 氢给体数：
  0
• 氢受体数：
  4

制备方法与用途

JZP-361是人类重组MAGL（hMAGL，IC50=46nm）的有效可逆抑制剂，其选择性比人类重组脂肪酸酰胺水解酶(hFAAH, IC50=7.24μM)高近150倍，比人类α/β-水解酶-6(hABHD6, IC50=1.79μM)高35倍。JZP-361是一种兼具MAGL抑制和抗组胺活性的双作用药理学工具[1]。

反应信息

• 作为产物：
  描述：

  氯雷他定 在 水 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 [4-(8-氯-5,6-二氢-11H-苯并[5,6]环庚[1,2-b]吡啶基-11亚烷基)-1-哌啶基](1H-1,2,4-三唑-1-基)甲酮
  参考文献：
  名称：

  Loratadine analogues as MAGL inhibitors

  摘要：

  Compound 12a (JZP-361) acted as a potent and reversible inhibitor of human recombinant MAGL (hMAGL, IC50 = 46 nM), and was found to have almost 150-fold higher selectivity over human recombinant fatty acid amide hydrolase (hFAAH, IC50 = 7.24 mu M) and 35-fold higher selectivity over human alpha/beta-hydrolase-6 (hABHD6, IC50 = 1.79 mu M). Additionally, compound 12a retained H-1 antagonistic affinity (pA(2) = 6.81) but did not show cannabinoid receptor activity, when tested at concentrations <= 10 mu M. Hence, compound 12a represents a novel dual-acting pharmacological tool possessing both MAGL-inhibitory and antihistaminergic activities. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.02.037

文献信息

• Cannabinoid receptor agonists and serine hydrolase enzyme inhibitor based anxiolytic therapeutic product
  申请人：Medipure Pharmaceuticals Inc.

  公开号：US11147805B2

  公开（公告）日：2021-10-19

  Provided herein are formulations for treating affective mood disorders. The formulations comprise one or more than one CB receptor agonist and one or more than one serine hydrolase enzyme inhibitor.

  本文提供了用于治疗情感性情绪障碍的制剂。这些制剂包括一种或多种 CB 受体激动剂和一种或多种丝氨酸水解酶抑制剂。
• CANNABINOID RECEPTOR AGONISTS AND SERINE HYDROLASE ENZYME INHIBITOR BASED ANXIOLYTIC THERAPEUTIC PRODUCT
  申请人：Medipure Pharmaceuticals Inc.

  公开号：EP3920925A1

  公开（公告）日：2021-12-15
• [EN] A GPR119-BASED SIGNALING SYSTEM IN THE MURINE EYE REGULATES INTRAOCULAR PRESSURE IN A SEX-DEPENDENT MANNER<br/>[FR] SYSTÈME DE SIGNALISATION À BASE DE GPR119 DANS L'ŒIL MURIN RÉGULANT LA PRESSION INTRAOCULAIRE EN FONCTION DU SEXE
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2017222713A1

  公开（公告）日：2017-12-28

  Methods of activating a GPR119-based signaling system in the mammalian eye are disclosed. More particularly, activation of the GPR119-based signaling system has been found to reduce intraocular pressure (IOP) in female mammalian eyes, providing a potential treatment for glaucoma.
• [EN] CANNABINOID RECEPTOR AGONISTS AND SERINE HYDROLASE ENZYME INHIBITOR BASED ANXIOLYTIC THERAPEUTIC PRODUCT<br/>[FR] AGONISTES DE RÉCEPTEURS DE CANNABINOÏDES ET PRODUIT THÉRAPEUTIQUE ANXIOLYTIQUE À BASE D'INHIBITEUR D'ENZYME SÉRINE HYDROLASE
  申请人：MEDIPURE PHARMACEUTICALS INC

  公开号：WO2020160677A1

  公开（公告）日：2020-08-13

  Provided herein are formulations for treating affective mood disorders. The formulations comprise one or more than one CB receptor agonist and one or more than one serine hydrolase enzyme inhibitor.
• Loratadine analogues as MAGL inhibitors
  作者：Jayendra Z. Patel、Stephen Ahenkorah、Miia Vaara、Marek Staszewski、Yahaya Adams、Tuomo Laitinen、Dina Navia-Paldanius、Teija Parkkari、Juha R. Savinainen、Krzysztof Walczyński、Jarmo T. Laitinen、Tapio J. Nevalainen

  DOI：10.1016/j.bmcl.2015.02.037

  日期：2015.4

  Compound 12a (JZP-361) acted as a potent and reversible inhibitor of human recombinant MAGL (hMAGL, IC50 = 46 nM), and was found to have almost 150-fold higher selectivity over human recombinant fatty acid amide hydrolase (hFAAH, IC50 = 7.24 mu M) and 35-fold higher selectivity over human alpha/beta-hydrolase-6 (hABHD6, IC50 = 1.79 mu M). Additionally, compound 12a retained H-1 antagonistic affinity (pA(2) = 6.81) but did not show cannabinoid receptor activity, when tested at concentrations <= 10 mu M. Hence, compound 12a represents a novel dual-acting pharmacological tool possessing both MAGL-inhibitory and antihistaminergic activities. (C) 2015 Elsevier Ltd. All rights reserved.